It is reasonable to begin a study of the neural mechanisms of pruritus with an analysis of how itch is signaled by the peripheral nervous system. It is not known which cutaneous receptors elicit itch. For the most part, classification of the receptors in mammalian skin is complete. Adequate stimulus requirements for many receptors have been documented, and each receptor population has been correlated with a particular cutaneous sensation. However, there is an exception. The sensation of itch has never been associated with a particular receptor population. Since itch is a unique sensory experience, there must be some characteristic mechanism by which it is encoded by the peripheral nervous system. There are two possible alternatives. (1) A receptor population has been missed. Because the peripheral nervous system has been carefully studied with electrical search stimuli, it is unlikely that a major receptor population has been overlooked. (2) There is a population of receptors that responds both to the itch-producing stimuli and to stimuli that elicit other sensations. In the present experiments, it is proposed to test these two alternatives by systematically recording single-unit activity from each type of cutaneous sensory neuron and applying itch-producing substances. Care must be taken first, to insure that the itch-producing substances are applied in a manner that will consistently induce pruritus; second, to determine whether other types of adequate stimuli can be presented to the receptor in ways that will mimic the receptor's response to itch-producing substances; and third, to insure that each type of primary afferent neuron has been adequately sampled. Because noxious stimuli induce both pain and itch, it is possible that both sensations might share some or all of the same sensory apparatus. Therefore, particular emphasis will be placed on testing "itch responsive" receptors with pain-producing stimuli in an effort to determine how the peripheral nervous system differentiates between these stimuli.